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Biomedical subjects

B A Reitz

Publications and source records attributed to B A Reitz.

At least 181 records · Page 10Linked to original sources

Physiologic aspects of human heart-lung transplantation. Pulmonary function status of the post-transplanted lung.

Pulmonary function measurements were performed before and after heart-lung transplantation in nine patients who had undergone surgery for end-stage pulmonary hypertension. In seven of them, sequential follow-up studies were performed at variable times postoperatively with the longest period 27 months. Pre-transplant studies showed a mild restrictive defect in 33 percent and obstructive disease in 50 percent of the patients, respectively. Arterial hypoxemia was present in all patients. The degree of mechanical changes found did not appear severe enough to account for the marked dyspnea and disability characterizing this group of patients with pulmonary hypertension. Following transplantation, all patients showed striking improvement of symptoms and general physical status. In the early post-transplant period, there was a marked decrease in most lung volumes resulting in a moderately severe restrictive ventilatory defect. Flow parameters that were reduced could be related to decreased volumes and not to intrinsic airway obstruction. Arterial O2 tensions improved dramatically and gas exchange was maintained at essentially normal levels. Lung function tended to improve progressively following transplantation with the passage of time. Heart-lung transplant is consistent with an adequate long-term pulmonary functional state which has the capacity to sustain the normal activities of daily living. From the standpoint of lung function, heart-lung transplantation appears to be acceptable as a form of therapy in selected patients.

Adult↗

Combined heart and lung transplantation.

Combined heart and lung transplantation was carried out in ten patients at Stanford University Medical Center between March, 1981, and December, 1982. All patients had end-stage pulmonary hypertension. 7 of them had Eisenmenger's syndrome and 3 primary pulmonary hypertension. 3 patients died within a month of operation, but the remaining recipients are well 2 months to 2 years after transplantation. The hospital stay of the survivors ranged from 38 to 85 days. All survivors have returned to normal activity. The results of heart and lung transplantation have thus been considerably superior to those reported previously for lung transplantation. It is suggested that cardiopulmonary replacement is suitable treatment for end-stage pulmonary hypertension with or without associated congenital heart disease and that its application to other forms of advanced pulmonary failure may be warranted.

Adult↗

Increased beta-adrenergic receptor density in an experimental model of cardiac transplantation.

We examined beta-adrenergic receptor density, basal, maximal isoproterenol and fluoride-stimulated adenylate cyclase activities, and morphologic characteristics of rabbit and rat native and heterotopic isograft cardiac tissue. Four weeks after graft placement there were only subtle histologic differences between native and graft tissue. Membrane preparations from isografts of rabbits demonstrated increases in beta-receptor density (maximum [3H]DHA binding = 111 +/- 19.3 fmol/mg versus 52.4 +/- 4.9 in native hearts, p less than 0.05). In a small number of experiments, rat isografts also demonstrated a suggestive increase in beta-receptor density (69.8 +/- 7.1 fmol/mg versus 40.2 +/- 7.3 in native hearts). Isoproterenol-stimulated adenylate cyclase activity was greater in rabbit graft hearts (3.98 +/- 0.20 X basal activity) than in native tissue 2.67 +/- 0.16 X basal activity, p less than 0.05). We conclude that cardiac denervation may lead to a postsynaptic form of beta-adrenergic supersensitivity that is due to an increase in beta-receptor density.

Adenylyl Cyclases↗

Diagnosis and treatment of allograft rejection in heart-lung transplant recipients.

Six patients received heart-lung transplants between March, 1981, and January, 1982. There were four women and two men between 26 and 45 years of age, three with primary pulmonary hypertension and three with congenital heart disease and pulmonary hypertension (Eisenmenger's syndrome). Immunosuppression was primarily with cyclosporin-A, with additional corticosteroid, azathioprine, and rabbit antihuman thymocyte globulin. Six episodes of allograft rejection in four patients (10, 11, 21, 24, 53, and 86 days after transplantation) were detected by means of transvenous endomyocardial biopsy. All patients experienced pulmonary edema early after transplantation (reimplantation response), and two patients required mechanical ventilatory support for allograft rejection at 10 and 11 days. Treatment of rejection consisted of intravenous methylprednisolone (four episodes) or augmented oral prednisone (two episodes), with resolution. No episode thought to be pulmonary rejection has occurred in the absence of cardiac findings. Four patients are alive from 6 to 15 months after transplantation and are functionally normal. Early experience with heart-lung transplantation suggests (1) that allograft rejection can be detected by cardiac findings and successfully treated by augmented corticosteroids, (2) that lung rejection does not occur in the absence of cardiac findings, (3) that the frequency and severity of rejection episodes are not greater than with standard cardiac transplantation, and (4) that the frequency of rejection episodes is highest within the first 60 days after transplantation.

Adult↗

Discriminant analysis of the changing risks of coronary artery operations: 1971-1979.

The risk of perioperative myocardial infarction (PMI) and operative mortality (OM) associated with coronary artery bypass grafting (CABG) has declined since the introduction of this procedure 15 years ago. Rigorous scientific investigation of the reasons for this trend has been hindered by the complex interactions between changing indications for operation, criteria for patient selection, and management methods. Using univariate and multivariate logistic regression analyses, we investigated the effects of 42 variables on PMI and OM for two cohorts undergoing CABG between 1971 and 1975 (Group A) and 1977 and 1979 (Group B). According to previously identified risk factors, Group B patients were at higher potential risk than those in Group A. Nevertheless, the PMI and OM rates declined from 8.7% +/- 0.9% to 4.6% +/- 0.7% (p = 0.005) and from 2.4% +/- 0.5% to 1.2% +/- 0.4% (p = 0.07), respectively. In calendar year 1979 (N = 438), the PMI and OM rates were 2.8% +/- 0.8% and 0.7% +/- 0.4%. More importantly, the independent determinants of PMI and OM for the two time intervals were distinctly different. Factors which affected the PMI rate in Group A were no longer determinants of PMI in Group B; with the exception of emergency operation and, to a modest extent, congestive heart failure (CHF), predictors of OM in Group A were not determinants of OM in Group B. Thus the adverse impact of multiple patient-related and disease-related determinants of PMI and OM has been neutralized over this decade by the real improvements in patient management. The specific factors and management concepts responsible for these superior results in sicker patients remain uncharacterized; however, in general terms, more sophisticated medical, anesthetic, and nursing management and more refined surgical expertise have essentially nullified the concept of high-risk candidates. Furthermore, the more propitious early results being attained currently may translate directly into parallel long-term improvements in functional benefit and survival.

Coronary Artery Bypass↗

Reappraisal of cardiopulmonary bypass with deep hypothermia and circulatory arrest for complex neurosurgical operations.

Although cardiopulmonary bypass (CPB) with hypothermia and circulatory arrest is routinely used for certain cardiovascular procedures, its advantages have infrequently been applied for other unusual surgical problems. Fourteen patients (six men and eight women, average age 48 years, range 29 to 74 years) underwent 15 operations over a 4-year period beginning in November 1978. Preoperative diagnosis included giant middle cerebral aneurysm (n = 8), internal carotid aneurysm (3), basilar artery aneurysm (2), and medullary hemangioblastoma (2). All patients had lesions that were considered inoperable by standard neurosurgical techniques. Operative technique consisted of peripheral cannulation with a long and short femoral vein cannula for venous return (24 to 28F) and a single femoral arterial cannula (18 to 24F). CPB flows ranged from 1 to 3.5 L/min, and the total CBP times averaged 146 minutes (range 66 to 282 minutes). Circulatory arrest times averaged 21 minutes (range 5 to 51 minutes), with two patients having no period of circulatory arrest. Lowest core temperature ranged from 16 degrees to 20 degrees C, with cooling and rewarming aided by Brown-Harrison heat exchangers placed in a countercurrent fashion within the venous return line. The heart spontaneously defibrillated in six patients, and external countershock was required in nine patients. No difficulty was encountered with cardiac distention. The intended operation was accomplished in all cases with 13 of 14 patients being discharged from hospital, having had a good neurosurgical result. One patient sustained a hemorrhagic infarction of the cerebellum and pons and is presently recovering. Our experience indicates that peripheral CPB with induced hypothermia and circulatory arrest is a safe technique for approaching otherwise inoperable neurosurgical lesions.

Adult↗

Heart-lung transplantation: successful therapy for patients with pulmonary vascular disease.

We report our initial experience with three patients who received heart-lung transplants. The primary immunosuppressive agent used was cyclosporin A, although conventional drugs were also administered. In the first patient, a 45-year-old woman with primary pulmonary hypertension, acute rejection of the transplant was diagnosed 10 and 25 days after surgery but was treated successfully; this patient still had normal exercise tolerance 10 months late. The second patient, a 30-year-old man, underwent transplantation for Eisenmenger's syndrome due to atrial and ventricular septal defects. His graft was not rejected, and his condition was markedly improved eight months after surgery. The third patient, a 29-year-old woman with transposition of the great vessels and associated defects, died four days postoperatively of renal, hepatic, and pulmonary complications. We attribute our success to experience with heart-lung transplantation in primates, to the use of cyclosporin A, and to the anatomic and physiologic advantages of combined heart-lung replacement. We hope that such transplants may ultimately provide an improved outlook for selected terminally ill patients with pulmonary vascular disease and certain other intractable cardiopulmonary disorders.

Adult↗

The use of 111In-labeled lymphocyte imaging to evaluate graft rejection following cardiac transplantation in dogs.

Lymphocytes separated from venous blood from six dogs who had heterotopic cardiac transplants have been labeled using 111In-oxine. Labeled lymphocytes were reinjected into the dogs and imaging of the heart carried out over the successive 3 or 4 days. For comparison serial ECGs and punch biopsies of the heart were obtained. Abnormal uptake of labeled lymphocytes in the donor heart was clearly visible in three of the six dogs, faintly visible in two and not seen in one. 630 mu Ci 111In was used in the dog where no uptake was seen and subsequent studies showed this amount of the radiopharmaceutical was toxic to lymphocytes. In the remaining five dogs the mean ratio of uptake of 111I in donor to recipient heart was 14:1 (range 6.5:1--21:1). The lack of substantial uptake in the transplanted heart of two dogs in attributed to a delay in rejection relative to the time the labeled lymphocytes were injected. The results suggest that 111In-labeled lymphocytes have potential as a noninvasive test for detecting rejection of cardiac transplants.

Animals↗

Cardiac transplantation in perspective for the future. Survival, complications, rehabilitation, and cost.

Two hundred twenty-seven cardiac transplant procedures have been performed in 206 patients from January, 1968, to April, 1981. Postoperative survival rates, calculated by the actuarial method for program years 1968 to 1973 (66 patients), are 44%, 33%, 27%, 21%, and 18% at 1, 2, 3, 4, and 5 years after transplantation, respectively. Postoperative survival rates for program years 1974 to 1981 (140 patients) are 63%, 55%, 51, 44%, and 39% at 1, 2, 3, 4, and 5 years after transplantation, respectively. This increase results primarily from improvement in survival achieved in the first 3 postoperative months (59% +/- 7%, 1968 to 1973, versus 80% +/- 40%, 1974 to 1980), reflecting improved patient management. Infection remains the primary cause of death following transplantation (76/131 patients, 58%), followed by acute rejection (24/181, 18.3%), graft arteriosclerosis (14/131, 10.7%), and malignancy (6/131, 4.6%). The development of graft arteriosclerosis has been examined in 85 one-year survivors studied by annual coronary arteriograms. Coronary lesions of varying severity have developed in 21 patients. HLA-A2 incompatibility was associated with a higher incidence of graft arteriosclerosis than was apparent for all other A locus incompatibilities (p less than 0.0003). Lymphoma has been shown to be associated with younger recipient age, a primary disease diagnosis of idiopathic cardiomyopathy, and retransplantation. One hundred six patients have survived at least 1 year after transplantation; 97% were in NYHA Class 1 at that time interval and 82% returned to employment or activity of choice. The longest survival time is new 11 years, 3 months. Cardiac transplantation can be considered "reasonable and therapeutic treatment to extend life" in selected individuals.

Actuarial Analysis↗

Ultrastructural and functional studies on prolonged myocardial preservation in an experimental heart transplant model.

The effect of ischemia with hypothermic cardioplegic preservation were studied in a heterotopic isograft rat heart transplant model. Hearts with ischemic time periods of 0.5, 4, 8, and 12 hours (n = 5 to 7 transplants per ischemic time period) were analyzed for structural and functional changes 50 days after transplantation. Postoperative recovery was prolonged with increasing duration of preservation times, but all transplants functioned normally 20 minutes and 50 days after transplantation. Function of right ventricular strips from graft and normal hearts were compared in a muscle bath. No differences were observed between baseline or isoproterenol-stimulated myocardium from all grafts or normal hearts. Electron and light microscopy studies of right and left ventricle and ventricular septum samples demonstrated marked fibrosis at 4, 8, and 12 hours of preservation with no differences between the 4, 8 and 12 hour grafts. There were no other differences in other features examined, including necrotic, mitochondrial, I-band, contractility, nuclear, endothelial cell, or intracellular lipid changes. We conclude that (1) except for significant fibrosis, transplants have normal structure and function after 4, 8, and 12 hours of preservation, (2) in assessing the efficacy of hypothermic cardioplegic preservation, chronic structural changes are more sensitive than functional changes, and (3) hypothermic cardioplegic preservation is feasible up to 12 hours but fibrosis may be the ultimate limiting factor in man.

Animals↗